The overall objective of this research proposal is to determine the neurobiological basis of auditory hallucinations (AHs) of spoken speech. This syndrome produces high levels of distress and disability in patients with schizophrenia and other psychotic disorders. The research proposal is based on pilot studies using functional and structural MRI involving schizophrenic patients with AHs, nonhallucinating patients with schizophrenia, and normal control subjects. Functional MRI data suggest that coactivation of Broca's and Wernicke's area occurs during hallucination periods. A second fMRI study suggests that these two brain areas are excessively coupled in hallucinators compared to nonhallucinating patients and normal controls. Abnormal coupling between these two regions is hypothesized to arise from loss of intrinsic connectivity within Wernicke's region suggested by cortical thinning found in our pilot structural MRI study. Loss of intrinsic connectivity is predicted to increase salience of interactions between that region and Broca's area, which could produce hallucinated speech with percept-like characteristics. 40 patients with AHs, 20 patients without a recent history of AHs, and 20 normal control subjects will be studied. Specific Aim #1: Brain activation during hallucination periods will be shown to involve Broca's and Wernicke's regions in a neuroanatomic distribution that approximates but is distinct from activation associated with listening to external speech. Specific Aim #2: The neuroanatomic distribution of BOLD signal correlations referenced to Wernicke's region will be shown to converge with activation maps for hallucination periods. Specific Aim #3: Using BOLD signal correlations, Broca's area will be shown to be excessively coupled to Wernicke's area in patients with AHs when compared to nonhallucinating patients and normal controls. Specific Aim #4: Cortical thickness in superior temporal cortex will be shown to be decreased in hallucinators compared to the other two groups of subjects. In summary, the proposed research plan will establish new neuroimaging tools for delineating the neuroanatomic and physiological basis of AHs. These findings could advance our ability to develop more specific and efficacious treatments targeting this syndrome. [unreadable] [unreadable]